Effect of Bioactive Glass on the Remineralization of Caries Lesion: A Systematic Review

Asma Dokhi Al Hamazani¹, Aldanah Turki Alwoseamer², Hala Omar AlWasem², Hind Bin Mlafakh², Munirh Marjan AlMarjan^2*, Nawaf Khalid Alfhaed³, Badr Soliman Alhussain¹

¹Department of Dentistry, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

²Department of Dentistry, College of Dentistry, Riyadh Elm University, Riyadh, Saudi Arabia.

³Department of Dentistry, King Saud University, Riyadh, Saudi Arabia.

*Email: [email protected]

ABSTRACT

Bioactive glass's most well-known capacity is its bonding ability to bone and promoting bone development. The bioactive glass may mineralize dentine tubules for sensitive teeth to provide relief and prevent caries. Bioactive glass is an emerging therapy for regenerating damaged bone tissue after injury or illness. Its usefulness in the medical profession has led to its implementation in several areas. In 1969, a silicate glass made of sodium, calcium, and phosphorus was the first bioactive glass on the marketUsing the databases PubMed, Medline, and ScienceDirect, a comprehensive review of the literature spanning 2011 to 2022 was conducted. The keywords used were "bioactive glass" and "caries remineralization". 8 studies were included in this systematic review. However, most of them revealed that bioactive glass could not provide enough remineralization, especially when compared to fluoride. Although bioactive glass has shown encouraging signs of remineralization, its effectiveness is not to the standard produced by fluorides. Hence, there is a need to conduct further studies to reassure the importance of bioactive glass as a good replacement for fluoride.

Key words:Bioactive glass, Dental caries, Remineralization, Systematic review

INTRODUCTION

Caries are characterized by the loss of mineral content and the degradation of dental hard tissues, and biofilms control it. Demineralizing dental hard tissues results from acid production by cariogenic bacteria, resulting in an oral cavity with a low pH environment for a long time [1-3]. If the surface carious lesions are left untreated, they will eventually become cavities in the tooth [4].

Bioactive glass is an emerging therapy for regenerating damaged bone tissue after injury or illness. Its usefulness in the medical profession has led to its implementation in several areas. In 1969, a silicate glass made of sodium, calcium, and phosphorus was the first bioactive glass on the market. You may get bioactive glass in various forms, including silicate-based and phosphate-based varieties. From the standpoint of material characteristics, bioactive glass is an ideal material. Scaffolds, made of bioactive and biocompatible glass, are used in bone repair to provide a three-dimensional template for bone regeneration [5].

Bioactive glass's most well-known capacity is its bonding ability to bone and promoting bone development. Its high reactivity when in touch with a bone surface is an advantage in bone augmentation and repair. As a first step, putting the material in an aqueous solution causes the particles to adopt a mesoporous structure. The particles will then group together to create an enrichment layer that mimics the apatite substance found in bone and other hard tissues. A layer of hydroxyapatite is formed when ions are exchanged back and forth between the bioactive glass and the bone surface. In the process of repairing defects, sediments that resemble bone are deposited on the surface of the bone. What happens to teeth is analogous to what happens to bones. The bioactive glass may mineralize dentine tubules for sensitive teeth to provide relief [6].

When utilised as a dental paste, Novamin adheres to the tooth's surface as a bioactive glass and continuously deposits a natural crystalline hydroxyl carbonate. It is a biomimetic mineralizer since it imitates the natural mineralization procedures of the body. Calcium and phosphate ions are swiftly released from the bioactive glass particles when sodium ions from the particles undergo fast exchange with hydrogen cations (in the form of H3O+) in the saliva in the oral cavity, the aqueous environment around the tooth. As sodium is released at first contact with water, the pH of the immediate vicinity rises briefly [7]. The elevated pH aids in the precipitation of calcium phosphate from the additional calcium and phosphate ions supplied by the Bioactive Glass. These interactions eventually cause this layer to crystallize as hydroxycarbonate apatite (HCA). The interaction between the residual Novamin particles and the freshly formed HCA layer results in remineralization of the enamel surface and protection against further demineralization [8].

MATERIALS AND METHODS

A systematic literature review from 2011 to 2022 was performed using databases such as PubMed, Medline, and ScienceDirect. The keywords used were "bioactive glass" and "caries remineralization." PRISMA flowchart was used to describe the selection process of searched articles.

Table 1. Inclusion and exclusion criteria

Risk of bias assessment

The Cochrane risk of bias assessment method was used to assess the quality of the studies included.

Table 2. Summary of Cochrane Risk of Bias Assessment

RESULTS AND DISCUSSION

The results, objectives, participants, follow-up periods, materials of all included studies are described in Table 3.

Table 3. Summary of findings of selected studies

Twenty human molars were acquired by Narayana et al. [9], all of which had to be extracted due to periodontal disease. The participants are divided into five distinct groups. Those in group A were given no treatment (the control), those in group B received fluoride toothpaste (Amflor), those in group C received tooth mousse, those in group D received tooth mousse plus, and those in group E were given a demineralized sample. One-way analysis of variance revealed that the group means were significantly different from one another. After ten days, all test groups were analysed using human hair spherical electron microscopy (HRSEM) and quantitative evaluation using energy dispersive X-ray spectroscopy (EDXR). The data were analysed using one-way analysis of variance (ANOVA), a student's t-test, and Tukey's multiple comparison tests. Alaudin and Fontana came to the conclusion that Novamin dentifrice resulted in significantly more remineralization than fluoride dentifrice based on their confocal laser scanning microscope investigation. Between Group A and Group B, there was a statistically significant difference, indicating that Group A had a higher amount of remineralization. Calcium was found to have much higher atomic and weight percentages than the control. Mineral deposits were seen along the porous flaws in a consistent distribution in the HRSEM image. The absence of evidence suggests that bioactive glass has no effect. Hence the alternative hypothesis that it does must be accepted. There was a smaller atomic and weight proportion of fluoride in Group C compared to Group B and Group D. This is supported by the fact that Novamin (SHY-NM) is not a fluoride-containing product.

According to Mehta et al.'s (2014) study [10], 30 human premolars in good health were extracted and used in an orthodontic investigation. Similar to how it had been done for B-SMH, VMT was utilised to confirm R-SMH. Following that, we divided the samples equally between the two groups (n = 15) using a random number generator. Dental products were divided into Groups A and B based on whether they contained BAG (SHY-NM; Group Pharmaceuticals; India) or CPP-ACP (GC tooth mousse; Recaldent; GCcorp; Japan). The pH was cycled daily for ten days. We measured the SMH of remineralized samples. The Bonferroni procedure was used for multiple comparisons within groups after an analysis of variance was performed (post-hoc tests). The researchers show us the differences in microhardness between Group A and Group B at each time point. There was no statistically significant difference in the two groups' mean microhardness before and after demineralization (P > 0.05). This suggests that the tooth samples were all very close in hardness following demineralization, which would provide a null result in statistical analysis. Changes in the mineralization of the tooth samples were shown by a significant difference in mean microhardness between the groups following remineralization (P 0.05).

The research performed by Rajendran et al. (2019) [11] shows that 45 permanent human premolar teeth were gathered, all of which had been recently removed (for orthodontic purposes). Demineralization using McInnes demineralizing solution was performed on all samples from groups I, II, and III. The mean and standard deviation were determined by using descriptive statistics. The Kruskal-Wallis, one-way analysis of variance, and Mann-Whitney U tests were used for the testing. Normal toothpaste without any remineralizing additives was part of the remineralization routine. A topical lotion comprising casein phosphopeptide-amorphous calcium phosphate was applied by Group III (n = 15). The toothpaste used by Group II (n = 15) contained calcium sodium phosphosilicate (Novamin). We analysed the topographical enamel surface pictures and energy dispersion of all the healthy samples under a scanning electron microscope. Calculated mineral (calcium and phosphorus) levels were estimated quantitatively across all three groups using X-ray analysis. In Group II, the average calcium and phosphorus levels for healthy enamel were 65.27 0.58 and 20.79 0.78, respectively. The average calcium and phosphorus levels in the deionized water were 55.09 0.54 and 15.71 0.57, respectively. Mean calcium and phosphorus values obtained after remineralization of the demineralized specimen with novamin-containing toothpaste were 61.29 0.62 and 17.56 0.43, respectively; these values were greater than those of the demineralized samples and statistically significant (p 0.001). When the mean calcium and phosphorus levels of the groups were compared, statistically significant differences were found, with group III having the highest mean calcium and phosphorus levels and group I having the lowest.

Remineralizing early-stage lesions and lowering the salivary S mutants load are significantly more effective with CPP-ACP-TF combination treatment using CPP-ACP/Xylitol/Bioactive glass/Ozone in addition to Topical Fluoride than with TF mono-therapy, according to Sharda et al. (2021) [12]. The main analytical methods employed in this investigation were quantitative light-induced fluorescence (QLF), visual inspection, and laser fluorescence. The remineralization potential is calculated using the results they offer. The results also demonstrate that combining xylitol and fluoride therapy can more effectively stop caries from progressing. It is impossible to comment on the increased caries prevention effectiveness of bioactive glass over fluoride alone due to a lack of scientific evidence. The combination treatment, however, was demonstrated to be superior when two trials were combined and WSL's regression was assessed visually using the Gorelick Index. When comparing the remineralization capacity of CPP-ACP-TF to that of TF monotherapy, as assessed by QLF, the current study indicated no statistically significant difference between the two groups. The release of Ca2+, Na+, PO43, and Si4 ions, which increases the local pH and osmotic pressure, is attributed to the possible use of calcium sodium phosphor-silicate (Bioactive glass/NovaMin) for caries prevention. The one clinical trial that was relevant to this meta-spectrophotometer analysis revealed no discernible difference between fluoride-only toothpaste and toothpaste including bioactive glass in terms of post-intervention visual change.

24 extracted human teeth were donated for this study by Alhussain et al. (2018) [13], who conducted their research at the College of Dentistry at Imam Abdulrahman bin Faisal University in Dammam, Saudi Arabia. For statistical comparisons between the three groups, the Kruskal-Wallis test was applied. The surface micro-hardness was assessed using a tool known as a Vickers tester. Between post-remineralization and post-demineralization readings, Group 3 had the highest difference (mean VHN = 118.73), followed by Group 2 (mean VHN = 60.54), and Group 1 (mean VHN = 47.44). The BioMin F group fared better than the other two groups at remineralizing the demineralized enamel structure, although neither group's structure could be restored to baseline levels with 800 strokes. Additionally, statistically significant (p 0.05) differences were seen in all groups when comparing values before and after demineralization and remineralization.

The goal of the study by Körner et al. (2020) [14] was to assess and compare the impact of two different bioactive glasses on the remineralization behaviour of initial caries lesions using 100 bovine enamel samples randomly divided into five groups of 20 samples each. The two bioactive glasses were hydroxyapatite-containing, fluoride-free Toothpaste (HTP) and fluoride toothpaste (FTP). For the statistical study of integrated mineral loss, Kruskal-Wallis and post hoc Conover tests were employed. This study's findings provide credence to this theory since remineralization was dramatically reduced in the bioactive glass groups compared to those to which just the FTP was applied. The FTP + BGnano and FTP + BGamorph groups underwent an additional application procedure of the bioactive glass slurry in contrast to the NC, HTP, and FTP groups, who received no additional intervention, so it is crucial to keep in mind that there is a potential for bias introduced by this fact.

This research by Kim et al. (2021) [15] aimed to assess the effectiveness of an experimental varnish containing bioactive glass (BAG) on enamel remineralization. Each of the eight treatment groups contained thirteen samples of enamel. Microhardness tests (n = 3), field emission scanning electron microscopy (FE-SEM) in conjunction with energy dispersive X-ray spectroscopy (EDS) (n = 5), and X-ray diffraction (XRD) analyses (n = 5) were carried out to assess the remineralization impact of three varnishes with and without ultrasonication. The findings of the microhardness test were examined using a one-way analysis of variance and Tukey's post hoc comparison (P 0.05). Three varnishes significantly increased the microhardness of demineralized enamel (P 0.05). Out of the three varnishes examined, the one with the BAG had the strongest microhardness, according to an experiment (P 0.05). Tooth Mousse and BAG-containing varnish groups both experienced a decrease in microhardness after ultrasonication (P 0.05). After examining three different varnishes, field emission scanning electron microscopy (FE-SEM) and X-ray powder diffraction (XRD) revealed precipitates of either hydroxyapatite (HAP) or fluorapatite (FAP) crystals. Remineralizing early carious lesions or a demineralized enamel surface may be possible therapeutically using the novel experimental varnish that contains BAG.

The purpose of the study by Hsu et al. (2021) [16] was to examine the effects of adding fluoride and/or bioactive glass (NovaMin) on the remineralization of hydroxyapatite (HA) discs, which are intended to mimic the enamel surface of real teeth. Surface morphologies were analyzed using scanning electron microscopy (SEM), and surface compositions were analyzed with X-ray photoelectron spectroscopy (XPS). There was a total of 22 hydroxyapatite (HA) discs ("Ca5(PO4)3(OH)") used in the experiment. Phosphoric acid was used to etch HA discs. Then the discs were treated with four different kinds of toothpaste: One Sensodyne toothpaste has fluoride, two Sensodyne toothpastes contain fluoride and bioactive glass (NovaMin), three Tom's toothpastes don't contain fluoride or bioactive glass (NovaMin), and four Tom's toothpastes do (NovaMin). The engraved discs were treated with various toothpastes for 15 days, once per day for two minutes. SEM was used to evaluate surface morphologies, and X-ray photoelectron spectroscopy (XPS) was used to determine surface composition. Among the three groups, Tom's Toothpaste with only NovaMin demonstrated the highest level of remineralization. Tom's toothpaste has peculiar qualities because it contains bioactive glass (NovaMin) (group 4). The etched HA crystals grew noticeably closer to one another, much as the fluoride-containing (group 1) and fluoride plus bioactive glass-containing (NovaMin) (group 2) toothpastes induced the HA crystals to grow closer to one another and create granules between the crystals. Additionally, the etched HA crystals' form changed or grew, indicating significant remineralization.

The human body contains the minerals sodium, calcium, phosphorus, and silica (sodium calcium phosphosilicate), which can also be found in bioactive glass. The ions released by bioactive glass immediately form hydroxycarbonate apatite (HCA), bypassing the intermediary ACP phase, which other calcium phosphate methods require. These particles adhere to the teeth, releasing ions and remineralizing the enamel even after the treatment has ended. In-vitro studies have demonstrated that these particles may release ions and convert them into HCA for up to two weeks. [17] The particles will eventually crystallize into hydroxyapatite; the mineral used to construct teeth and bone. It is hypothesized that the HCA layer aids in the remineralization of teeth. Bioactive glass experiences an instantaneous three-stage surface reaction in a water environment that includes leaching and exchanging cations, network SiO2 dissolution, and the precipitation of calcium and phosphate to create an appetite layer. There is evidence to suggest that bioactive glass may help restore lost minerals. Therefore we must reject the null hypothesis and go on. There was a smaller atomic and weight proportion of fluoride in Group C compared to Group B and Group D. This is true since Novamin (SHY-NM) is a non-fluoridated alternative to regular toothpaste. The availability of fluoride is crucial for its caries-preventive action. The dissolution of the fluoride-containing substance and its adherence to the surface determine the bioavailability of fluoride. Sodium fluoride, sodium monofluorophosphate, and amine fluoride are the most common fluoride formulations utilized as carriers for fluoride ions in dentifrices. Amine fluoride's impact on enamel remineralization has been the subject of laboratory and human studies. The solubility of NaF, sodium monofluorophosphate, and amine fluoride may have an impact on the bioavailability of fluoride in saliva as well as the demineralization and remineralization potential of enamel [18].

In the current investigation, two dentifrices that are not typically the primary active components in widely used dentifrices were compared for their remineralization capacity. Examining changes in the surface layer is important due to the relevance of this area in caries development; consequently, SMH measurement is an appropriate tool for investigating the de-remineralization process. Microhardness testing is the best option for materials with a fine microstructure, non-homogeneity, or brittleness to cracking. Studying the effects of demineralization and remineralization using SMH indentations is quick, easy, and doesn't damage the hard surface.

Three studies [19-21] were combined to analyze the effects of CPP-ACP-TF combination therapy on fluorescence and lesion area, including 105 individuals in the treatment group and 118 in the control group. Neither the DF nor the lesion area was significantly different after the intervention. Pooling of two trials [19, 22] utilizing the general inverse variance approach to evaluate the visual change in WSLs according to the Gorelick criterion. When comparing the efficacy of fluoride mono-therapy vs. the CPP-ACP-TF combination, it was shown that the latter was superior in reducing the WSLs.

For the objective of remineralization, participants in Group II in the current research utilized a toothpaste containing bioactive glass (novamin). Casein phosphopeptide-amorphous calcium phosphate was applied topically to group III. Caries models have shown that CPP-ACP nanocomplexes effectively prevent and reverse enamel defects. CPP-ACP effectively halts enamel demineralization and stimulates remineralization in its earliest stages. Clinical in situ experiments demonstrated a remineralizing impact on teeth for a limited time, and an in vivo randomized control study demonstrated a caries-preventing efficacy over the long term [23]. ACP is not only held in place by the CPP, but it is also delivered to the tooth surface and kept there by the CPP [24]. The location of amorphous calcium phosphate on the tooth surface, where it buffers the free calcium and phosphate ion activities, is thought to be how CPP-ACP exerts its anti-cariogenic effects. This helps to keep the tooth enamel supersaturated, which prevents demineralization and promotes remineralization [25].

The present surface micro-hardness research indicated that, compared to fluoride-based toothpaste and distilled water, BioMin F toothpaste had a greater remineralizing effect. Because of its unique chemical makeup, BioMin F has more remineralization capability than regular fluoride toothpaste. Calcium sodium phosphosilicate (BG) is the typical formula and does not include fluoride. Fluoride may be found in the BioMin F toothpaste's BG formula, which is strong in phosphate [26]. When BG is placed in the mouth, ionic exchange activities take place, leading the glass to dissolve and release calcium (Ca2+) and phosphate (PO4-) ions, which results in the development of FAP, which is more acid-resistant and is particularly desirable for a number of dental applications. Since it helps to maintain the glass's network connection and ensures the production of FAP, it has been demonstrated that the high phosphate content of BG toothpaste is advantageous [27].

The current investigation shows that when bioactive glasses were employed in addition to brushing with 1,400 ppm FTP, remineralization was significantly reduced. The Schott bioactive glass is a typical amorphous bioactive glass that has received praise for its capacity to remineralize and strengthen human hard tissue as well as help repair enamel erosion brought on by acid by releasing ions that can build a mineral matrix similar to hydroxyapatite. The bioactive glass employed in Actimins appears to have SiO2 as its crystalline phase, and the glass contains a bioactive, nanocrystalline powder. Actimins describes itself as a de-sensitizer that also purports to raise intraoral pH, release minerals (silica, calcium, and phosphorous), and crystallise a developing calcium and phosphate layer into carbonated hydroxyapatite, aiding tooth remineralization. The hardness of the enamel surface is greatly increased by bioactive glasses [28].

The ability of BAG to remineralize enamel has been the subject of much research. It has been observed that the microhardness of the enamel surface degraded from below by 45S5 BAG paste has increased. Studies have shown that applying BAG paste to early-stage enamel erosion lesions forms an abrasion-resistant layer of HAP [29]. Studies on remineralizing carious-like lesions in permanent teeth found that BAG-containing toothpaste was more effective than fluoride-containing toothpaste [30]. Caries in primary teeth were remineralized by BAG much as they were by CPP-ACP and Toothpaste containing 500 ppm fluoride. Previous research has shown that BAG is most often applied as a paste. Unfortunately, the enamel surface lacks the substantivity necessary for this shape [31].

To demineralize the enamel, 40% phosphoric acid was used to etch the HA discs. As was to be expected, Tom's fluoride-free and NovaMin-free Toothpaste failed to stimulate remineralization since it lacked essential ingredients. Tom's of Maine fluoride-free and NovaMin-free toothpaste contains hydrated silica for polishing and cleansing and sodium bicarbonate for breath freshening and whitening. In their research, Hamza et al. tested several kinds of toothpaste' abrasiveness and cleansing power. Hydrated silica was more abrasive than other abrasives [32]. This might help explain our observation that Tom's toothpaste and etched HA discs have comparable geometries.

CONCLUSION

Although bioactive glass has shown encouraging signs of remineralization, its effectiveness is not to the standard produced by fluorides. Hence, there is a need to conduct further studies to reassure the importance of bioactive glass as a good replacement of fluoride.

ACKNOWLEDGMENTS : We would like to acknowledge the help of Riyadh Elm University research center.

CONFLICT OF INTEREST : None

FINANCIAL SUPPORT : None

ETHICS STATEMENT : This study fulfills the ethical requirements of Riyadh Elm University.